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. 2021;55(9):860-875.
doi: 10.1007/s11094-021-02510-0. Epub 2022 Jan 13.

Potential for the Development of a New Generation of Aminoglycoside Antibiotics

A N Tevyashova  1 , K S Shapovalova  1
Affiliations

Potential for the Development of a New Generation of Aminoglycoside Antibiotics

A N Tevyashova et al. Pharm Chem J. 2021.

Abstract

The present review summarizes recent publications devoted to aminoglycosides that study the main types of resistance to antibiotics of this class and the main directions of chemical modification aimed at overcoming the resistance or changing the spectrum of biological activity. Conjugates of aminoglycosides with various pharmacophores including amino acids, peptides, peptide nucleic acids, nucleic bases, and several other biologically active molecules and modifications resulting in other types of biological activity of this class of antibiotics are described. It is concluded that a promising research direction aimed at increasing the activity of antibiotics against resistant strains is the search for selective inhibitors of aminoglycoside-modifying enzymes. This would allow renewal of the use of antibiotics already meeting widespread resistance and would increase the potential of a new generation of antibiotics.

Keywords: aminoglycoside antibiotics; chemical modification; drug resistance; mechanism of action; structure–activity relationship.

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Figures

Fig. 1.
Fig. 1.
Structures of series of aminoglycoside antibiotics.
Fig. 2.
Fig. 2.
Specificity of several aminoglycoside-modifying enzymes.
None
Scheme 1
Fig. 3.
Fig. 3.
Action of aminoglycoside-modifying enzymes on plazomicin.
Fig. 4.
Fig. 4.
Structures of arginine–aminoglycoside conjugates.
Fig. 5.
Fig. 5.
Structure of neamine–PNA conjugate.
Fig. 6.
Fig. 6.
Structures of neamine–PNATAR conjugates.
Fig. 7.
Fig. 7.
Structures of neamine–amino-acid–nucleotide (12, 13) and neamine–amino-acid–pyrene conjugates (14).
Fig. 8.
Fig. 8.
Structure of neomycin–thymine conjugate.
Fig. 9.
Fig. 9.
Structures of neomycin (16a-e) and paromomycin conjugates (17a-e) with nitrogenous bases.
Fig. 10.
Fig. 10.
Structures of neomycin conjugates with natural and synthetic nucleic bases.
Fig. 11.
Fig. 11.
Structures of neamine (19) and ribostamycin conjugates (20) with oligonucleotides.
Fig. 12.
Fig. 12.
Structures of neomycin and dinucleotide conjugates.
Fig. 13.
Fig. 13.
Structure of antifungal drug K-20.
Fig. 14.
Fig. 14.
Structures of inhibitors of connexin HCs.
None
Scheme 2
Fig. 15.
Fig. 15.
Structure of 5”-deoxy-5”-formamidopropylamycin.
See this image and copyright information in PMC

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